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Human keratinocytes release high levels of inducible heat shock protein 70 that enhances peptide uptake
Author(s) -
Wang Dong,
EizVesper Britta,
Zeitvogel Jana,
Dressel Ralf,
Werfel Thomas,
Wittmann Miriam
Publication year - 2011
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2011.01287.x
Subject(s) - hsp70 , heat shock protein , peptide , psoriasis , flow cytometry , cytokine , keratinocyte , human skin , chemistry , microbiology and biotechnology , biology , immunology , in vitro , biochemistry , gene , genetics
Background: The stress‐inducible chaperone heat shock protein (HSP) 70 is considered a ‘danger signal’ if released into the extracellular environment. It has been proposed to play a role in the pathogenesis of skin diseases such as psoriasis and lupus erythematosus (LE). Objectives: The aim of this study was to decipher the role of human primary keratinocytes with regard to release and reactivity to HSP70. Methods: We determined HSP70 and IFNγ in cell supernatants by ELISA. Uptake of labelled HSP70 or labelled peptide by human primary keratinocytes or macrophages was analysed by flow cytometry and fluorescent microscopy. Results: We found that living keratinocytes are an important source of HSP70 in the skin compartment. They release considerably more HSP70 than fibroblasts, macrophages or lymphocytes. Interestingly, keratinocytes also bind and internalise HSP70/HSP70–peptide complexes. TNFα, IL‐27 as well as HMGB‐1 enhanced the uptake of HSP70. No difference with regard to HSP70 release or uptake was observable between keratinocytes from healthy donors or patients with cutaneous LE. Keratinocytes pulsed with HSP70–peptide complexes significantly increased IFNγ production by autologous T cells. Conclusions: Production and uptake of inducible HSP70 by keratinocytes may critically influence the chronic course of inflammatory skin diseases.